Gastritis: Its Clinical Significance: With Special Emphasis on the Tumor-Simulating Variety

Gastritis: Its Clinical Significance With Special Entphasis on the TUlllor-Sintulating Variety M. A.

SI)EIJ~BERG,

M.D., F.A.C.P. *

L:ESTER BAK:ER, M.D. **

WITH the introduction of the flexible gastroscope much interest was directed toward the problem of gastritis. This was to be expected since gastritis is the most frequent gastroscopic diagnosis, and most of the gastritides can be diagnosed only gastroscopically. This led to a sharp dispute as to the clinical importance and symptomatology of gastritis. We are of the opinion that many varieties of gastritis may exist without the production of symptoms, and symptoms present may not depend solely.or at all on this gastric lesion. However, some cases of severe superficial gastritis and hypertrophic gastritis may be productive of symptoms or even hemorrhage. l"he gastritis of the postoperative stomach may contribute to the postgastrectomy symptoms and finally certain types of gastritides may mimic carcinoma and may possibly be precancerous lesions. rrhis paper ,vill emphasize the problems involved in the tumor-simulating gastritis.

CLASSIFICATION

Gastritis may be classified as follows: A. Acute gastritis 1. Superficial Exogenous-alcoholic; secondary to pyloric obstruction, etc. Infectious-diphtheria, influenza, infectious hepatitis, etc. Allergic

* Associate Professor of M edicine, University oj Illinois College of Medicine; Associate Attending Physician, Michael lleese Hospital, Chicago, Ill.; Consultant in Medicine, H ines V eterans Hospital ~ H ines, Ill.

** Chief.oj Sect·ion of Gastroenterology, Hines lTeterans Hospital, Hines, Ill.; Instructor in Medicine, University of Illinois College of Medicine. Published with the approval of the Chief Medical Director, Veterans Administration. 'The staternents and conclusions published by the authors are the results of their own study and do not necessarily reflect the opinion or policy of the Veterans Adn~inistration.

41

42

M. A. /)pellberg, Lester Baker

2. Corrosive 3. Phlegmonous 66 B. Chronic Gastritides 1. Superficial 2. Atrophic Simple Atrophic hyperplastic-often producing tumor-simulating gastritis 3. Hypertrophic Simple Tumor-simulating C. Special Forms 1. Postoperative-especially postgastrectomy; a mixture of superficial and hypertrophic 2. Tumor-simulating-may either be a pronounced atrophic-hyperplastic gastritis or hypertrophic gastritis, localized or generalized 3. Postirradiation-a form of superficial gastritis, often leading to gastric atrophy 4. Gastric atrophy-most prominent in pernicious anemia

rfhe frequency of gastritis is emphasized by our experience at Hines Veterans Administration Hospital. Some form of gastritis was diagnosed 547 times in 886 gastroscopic examination. The hypertrophic variety was commonest while the su'perficial type was next in frequency. For the complete breakdown see Table 1. Table 1 CiASTRITIS AS SEEN IN

886

GASTROSCOPIC EXAMINATIONS

CARDIA

BODY

T~:~

MIXED TOTAL

106 Superficial 7 15 54 30 - - - - - - - 1 - - - _._.- - - - - - - - - - - 221 Hypertrophic 22 122 30 39 Isolated Gastritis

Atrophic

I

8

-20

-5---7-1-;-

Postoperative gastritis 67 Giant rugal folds. . . .. 13 Tumor-simulating gastritis. . . . . . . . . . .. 3 Antral gastritis. . . . . .. 43 Gastritis with J\..ssociated Lesions

367

Mixed gastritides 25 Gastric ulcer 14 Gastric carcinoma. . .. 13 Gastric diverticulum.. 2

126

54

Total. ... 547

SUPERFICIAL GASTRITIS

In this form of gastritis, the changes are limited essentially to the uppermost layers of the gastric mucosa. Superficial gastritis may occur

Gastritis: Its Clinical Significance

43

in either an acute or chronic form. A special form is secondary to high grade pyloric obstruction when peristalsis is still actively propelling food and gastric juice against the impenetrable pyloric canal. The resultant effect as seen gastroscopically is (1) hyperemia of a fiery red color, usually patchy, (2) adherent mucus, especially of the antrum, and/or (3) edema of a soft, boggy nature with increased highlights. Small erosions and petechial hemorrhages may also be present. It should be noted here that this appearance is indistinguishable from the mucosal changes noted by Wolf and W0lff 3 in response to emotional stress and, therefore, may be on occasion a transient functional change. Superficial gastritis has been described in staphylococcal food poisoning4' 5 and in infectious hepatitis. 6 , 7 In the latter disease mild hypertrophic gastritis has also been described. Spellberg and N orfleet 67 reported a case of severe superficial gastritis on the basis of secondary syphilis. Acute corrosive superficial gastritis may present a picture similar to that of chronic superficial gastritis. Necrosis and scab formation are additional findings followed by inflammatory reaction \vhich may become hemorrhagic. 10 Fibrotic scarring will frequently result in stenotic obstructive lesions later. ll Occasionally this occurs without involvement of the esophagus. 12 The latter is more likely if the corrosive is an acid. Gastroscopy is generally contraindicated in the acute stage of corrosive gastritis because of the danger of perforation. Superficial gastritis may change into chronic atrophic gastritis. rrhis has been reported by one of us (M.A.S.) following superficial syphilitic gastritis. 67 Superficial gastritis has never been noted to progress to hypertrophic gastritis. 13 It may occur as an isolated lesion, or engrafted on other forms of gastritis. rfhe latter occurs in the mixed superficial hypertrophic gastritis seen most often in the postoperative stomach. rfhe superficial form of gastritis may also occur with other lesions, such as gastric tumors or gastroduodenal ulcers. Histologically, the chief features of superficial gastritis are the subepithelial edema between the pits, resulting in mucosal thickening, plasma cell infiltration in the edematous area, and occasional red cell extravasations and superficial erosions. The atraumatic technic of obtaining biopsies of the stomach is very helpful in preventing confusion with the results of surgical trauma. 14 ATROPHIC GASTRITIS

Gastroscopically, atrophic gastritis is characterized by a gray or greenish-gray discoloration, patchy mucosal thinning, and visible submucosal blood vessels. The occurrence of the latter phenomenon is not specifically due to thinning of the overlying mucosa but rather to the characteristic early disappearance of the opaqu.e chief cells rendering the

44

M. A. Spellberg, I.Jester Baker

mucosa more transparent. Highlights are often increased and fine granular nodes may be seen. Large pseudopolypoid nodes may occur if reactive hyperplasia is marked. Mucosal hemorrhages and erosions may occur; the former never transform into the "pigment spots" so often seen in superficial gastritis. Histologically, atrophic gastritis is eharacterized by epithelial and exudative changes. l'here is atrophy of the glandular struetures and cysts may form as an aftermath of inflammatory compression of the neck of the glands. Between the pits the cellular infiltrate contains many plasma cells but if they extend down into the interglandular interspaces, lymphocytes predominate. The proliferation of pits starts early toward the muscularis mucosae and these may become tortuous and branching. 1"hus pseudopolyps may form. 'I'hese proliferative pits and remaining body glands occasionally undergo metaplasia to intestinal type epithelium-cells containing mucus, numerous goblet cells, many mitoses and typical Paneth cells. 'rhe muscularis mucosae is often involved in the inflammatory changes. Schindler feels that sometimes this inflammatory gastritis may eventuate in a true gastric atrophy. Atrophic gastritis is almost always found in stomachs containing carcinoma,l5 is constant and most severe in the stomachs of patients with pernicious anemia,16-19 the latter disease having been noted to be significantly associated with gastric cancer. 20 Atrophic gastritis has also been noted to be associated with benign gastric polyps,21 a condition generally accepted as potentially precancerous. It is also found in association with both duodenal and gastric ulcers, being a little more frequent and severe in the latter. Roentgen therapy, sometimes used for treatment of peptic ulcer, is often followed, after an initial superficial gastritis, by atrophy. It has been suggested that certain types of atrophic ga.stritides may predispose to gastric carcinoma,2o. 58 but the problem is not entirely settled. HYPERTROPHIC GASTRITIS

This form of gastritis as ,vell as atrophic gastritis is not known to occur in an acute form. Characteristically, hypertrophic gastritis represents a particular type of mucosal reaction with true proliferation without glandular atrophy, resulting in a thickening of the gastric mucosa. Gastroscopically, the mucosa is noted to be dull, velvety, granular, slightly swollen and "cobble-stone" in appearance, depending on the severity of the process. These changes first occur in the interrugal valleys and later involve the rugae. 1"he irregular, polygonal areas of "cobblestone" mucosa may be of different size and elevation so that gradative adjectives, such as granular, nodular and verrucous, have been applied. Thickening of rugal folds is not in itself a characteristic sign of hypertrophic gastritis. Ulcerations are frequently present and may attain considerable size-these ulcerations were always superficial.

Gastritis: Its Clinical

~'3ignificance

45

Histologically, three main types can be distinguished: 13 (1) Hypertrophic interstitial gastritis is an unusual type with mucosal thickening due to interglandular cellular infiltration, chiefly of small round cells. 2 The hypertrophic proliferative gastritis is occasionally mistaken grossly for early carcinoma. The glandular layer frequently comprises 33 to 50 per cent of the entire mucosal thickness, the increase being due to epithelial hyperplasia. I"fhe surfaee epithelium branehes freely, often producing cone-shaped buds. 1-'he cells contain little mucus and have many mitoses. The pits are elongated and there is an increased interstitial infiltration of polymorphonuclear and plasma cells. Huge cysts may form. The hypertrophic glandular gastritis at first glance appears normal histologically. Closer scrutiny reveals that the apparent folds contain no stalk and are not true folds but rather overgrown glands. The mucosal thickness may amount to 5 mm. or more. Between the pits, increased number of plasma cells and fibroblasts may be seen. Corkscrew-like pits and deep mucosal cysts may be found, the latter frequently containing polymorphonuclear leukocytes. The deeper layers of the last two types of hypertrophic gastritis are normal. In the interstitial type, the muscularis may be split and infiltrated and occasionally the submucosa may show infiltration. Benign pyloric obstruction frequently leadsto a hypertrophic gastritis, most often with a superimposed superficial gastritis. TUMOR-SIMULATING GASTRITIS

l'he term tumor-simulating gastritis emphasizes one of the clinical dilemmas of a peculiar type of gastritis, usually of the hypertrophic variety. It is also referred to as giant hypertrophic gastritis. Giant rugal folds which are otherwise normal may also simulate roentgenographically a gastric tumor. Maimon and co-workers,32 in 1947, reported 6 eases of giant hypertrophic gastritis, emphasizing some of the clinical, roentgenologic, gastroscopic and pathologic features of this condition. The x-ray findings which are the usual source of confusion show various sized filling defects on the greater curvature or in the midportion of the stomach which is caused by the markedly enlarged rugal folds. The folds may be nonpliable, not obliterated on pressure and appear to be accompanied' by local stiffness of the gastric wall. The stiffness of the gastric wall with collections of barium between the mucosal elevations resembles a polypoid carcinoma and makes the differential diagnosis extremely difficult. Certain features will, however, help in the differential diagnosis. Rarely is the lesser curvature involved. 30 Sprigg36 considered the maintained power of dilation and contraction and the presence of peristalsis through the involved area as characteristic of the benign lesion. Gastroscopically, an ill-defined bulge of th.e posterior wall is usually

46

M. A. Spellberg, Lester Baker

encountered, occasionally covered with normal mucosa but more frequently with the velvety mucosa of hypertrophic gastritis. The folds cannot be obliterated by inflation. 37 This "tumor" usually has sluggish peristaltic waves passing through it, although rarely it may move "en bloc." The surface may show superficial benign appearing ulcerations. 38 The large folds may be diffusely thickened, edematous and hyperemic (Fig. 6). The crests may show erosions with gray exudate, or as in one of our cases, umbilication with or without hemorrhage. This causes confusion with lymphosarcoma. These finger-like folds have been likened to sulci and gyri of the cerebral convolutions. 39 Round or oval polyps, usually sessile, may be seen. These are usually not well defined and may be distinguished from the true adenomas 4o which are frequently red,

Fig. 6. Gastroscopic appearance of giant rugal folds. The view on the left shows a patch of hypertrophic gastritis.

opaque, covered with a normal mucosa, often pedunculated, and frequently appearing on an atrophic background. The gastroscopic differentiation from malignancy may be troublesome but not quite as difficult as the roentgenographic differentiation. In two of our cases we made this error but in the third case the correct diagnosis was made. The resemblance is more to lymphosarcoma than carcinoma. Some cases of gastric lymphosarcoma may give the gastroscopic appearance of thickened, edematous rugal folds. 68 As a rule, the greater pliability and response to inflation of the folds in gastritis as well as the absence of necrotic ulcerations, and isolated tumor formations should help to distinguish the two entities. Grossly, the gastric wall is thickened and frequently shows prominent serosal vessels. The areas involved often feel softer than a neoplasm and have been likened to a "bag of worms." On opening the stomach, the rugae seem to form convolutions 41 , 42 (Fig. 12).

Gastritis: Its Clinical Significance

47

As to incidence, the condition has been reported rarely, only about 50 cases having been reported in the literature to 1950. 43 However, we are certain that many cases of severe hypertrophic gastritis have been mistakenly diagnosed clinically as gastric carcinoma, and not reported as a distinct entity of tumor-simulating gastritis. Nonetheless, the condition must be rare. Balfour44 found only 1 case in 8000 autopsies, while Eliason found only 2 in a similar number of autopsies. 45 Kantor 34 found 2 in 2500 x-ray examinations and Feldman35 one in 25,000 such examinations. Sprigg36 found 9 in 4424 x-ray examinations, only 3 of which were widespread. Marshall46 has stated that 6 cases have been recognized roentgenographically and at operation at Lahey Clinic. Maimon and his co-workers 23 found 10 in 5765 gastroscopies, 6 of which were confirmed, an incidence of 0.1 per cent. We have found 3 in 886 gastroscopies, all confirmed, an incidence of 0.34 per cent. The following 3 cases illustrate some of the problems encountered in tumor-simulating gastritis. CASE I. G. C. H. Admission 1: This 51 year old white man entered the hospital with residues of frostbite of the hands and a 30 pound loss of weight in the previous 6 months and increasing fatigability. There were no complaints directly referable to the gastrointestinal system. Physical examination revealed residues of frostbite but was otherwise essentially normal. The hemogram was within normal limits and the 'stools were negative for occult blood. A gastric analysis showed a rise of free acid to 24 units on histamine stimulation. Total serum protein was 5.6 gm. per 100 cc., with an albumin-globulin ratio of 3.5: 2.1. Liver function tests including cephalin flocculation, thymol turbidity, serum bilirubin, and bromsulphalein retention were normal. A roentgenologic examination of the upper gastrointestinal tract revealed what was interpreted as a fungating carcinoma of the stomach. Gastroscopy was performed and the antral rugal folds were noted to be large, hyperemic and edematous but not segmented or nodular. In the proximal portion of the pars media the mucosa was segmented, having a nodular appearance. In the fundus of the stomach on the greater curvature, a projecting nodular area was noted, which ran transversely across the gastric wall. This area was grayish yellow and was extremely suggestive of neoplastic tissue, although no ulceration was noted. The gastroscopic impression was severe nodular hypertropic gastritis of the proximal portion of the body of the stomach, with one area suggestive of neoplastic change. Gastroscopy was repeated 10 days later and was essentially unchanged. A note was made that this case was similar to those reported by Maimon and his associates. 23 Surgery was decided upon because of the roentgenographic picture and the difficulty in ruling out malignancy. The serum protein level was raised with plasma and high protein diet to 7.2 gm. per 100 cc. The stomach appeared normal on its exterior surface, but when it was opened the rugae were markedly hypertrophic and reddened. There was no gross evidence of malignancy. Histologic examination of the biopsy specimen revealed a severe hyperplastic gastritis, with increase in gland structure and cyst formation (Fig. 7) . Admission 2: This patient was readmitted to the hospital 6 months after the initial hospitalization, again complaining of weight loss and easy fatigabilitv.

48

M. A. Spellberg, Lester Baker

Again, the patient's total serum protein levels were subnormal and were raised to normal limits with plasma transfusion and high protein diet with supplements. Gastroscopy was repeated on two occasions and a marked improvement in the inflammatory reaction was noted at the second examination. X-ray examination (Figs. 8, 9), however, revealed little improvement in the size of the gastric folds. CASE 11. J. L. I. This 28 year old white male machinist entered the hospital complaining of easy fatigability of one year's duration and swelling of the legs of two days' duration. The physical examination failed to reveal any abnormalities except for a pitting edema of the ankles and lower third of the legs bilaterally.

Fig. 7 (Case I, G. C. H.). Microscopic section of gastric mucosa (X60) showing glandular hyperplasia, cyst formation, and pale mucus containing "intestinal type" of epithelium.

The hemogram was within normal limits and stools were negative for occult blood. A gastric analysis showed no free acid with a total acidity of 18 units. The total serum protein was 3.2 gm. per 100 cc. with an albumin-globulin ratio of 2.0: 1.2. This hypoproteinemia was improved to a level of 5.1 preoperatively by the use of multiple plasma transfusions, the albumin level being raised to only 3.2 gm. per 100 cc. Bromsulphalein excretion test showed no retention. A roentgenographic examination of the stomach revealed a filling defect of the greater curvature near the incisura. A second defect was noted in the body of the stomach and tremendous swelling of the folds were noted in the regi.on of the fundus. The impression was neoplastic infiltration of the stomach wall, probably lymphoblastoma. Gastroscopic examination revealed an aggregation of varying sized nodules just superior to the antral sphincter on the greater curvature. Some of these nodules were also noted on the lesser curvature. Some hemorrhagic areas were seen at the summit of the nodules within bleblike structures containing a slight depression. These hemorrhagic areas were described as being

Gastritis: Its Clinical ~,)ignificance

49

similar to the "projecting hemorrhages" sometimes described as diagnostic of lymphosarcoma. The gastroscopic impression was extensive lymphosarcoma of the stomach. An exploratory laparotomy was performed and the stomach wall on pal-

Fig. 8 (Case I, G. C. H.). Barium filled stomach showing large filling defects in body of stomach interpreted as fungating carcinoma.

Fig. 9 (Case I, G. C. H.). These x-rays were done two months after Figure 8. Filling defects in the stomach still noted.

50

M. A. Spellberg, Lester Baker

pation was described as feeling like a "bag of worms." On gastrotomy, the rugae were greatly hypertrophied and were polypoid. Many of the polypoid lesions were umbilicated with erosions of the mucosa at the tips. This polypoid change extended from the pylorus to within a few centimeters of the esophagus involving the entire fundus (Fig. 10). It was felt that this represented a multiple polyposis and a subtotal gastric resection was performed. Histologic examination revealed adenomatoid hyperplasia of the gastric mucosa, with increase in length and tortuosity of glandular structures, cyst formation, and absence of inflammatory cells (Fig. 11). X-ray postoperatively still showed some of the polypoid changes

Fig. 10 (Case 11, J. L. I.). Resected stomach showing large rugal folds resembling convolutions of brain.

in the gastric stump (Fig. 12). The patient improved after operation, and when last seen he was entirely asymptomatic with a total serum protein of 6 gm. per 100 cc., of which albumin constituted 4.2 gm. CASE Ill. J. H. A. This 55 year old Negro house painter entered the hospital with a history of periodic upper abdominal distress of 28 years' duration. There was no relation to food intake, but the distress was relieved by defecation and in the 2 months prior to admission to the hospital there had been alternate constipation and diarrhea associated with a 12 pound weight loss. The physical examination was essentially normal. The hemogram was within normal limits. Stools were negative for occult blood. A fractional gastric analysis with histamine stimulation failed to reveal any free acid.

Gastritis: Its Clinical Significance

51

Fig. 11 (Case 11, J. L. I.). Microscopic picture of gastric mucosa (X30) showing hyperplasia of gastric mucosa, tortuosity of glandular structures, absence of inflammatory cells.

Fig. 12 (Case 11, J. L. I.). X-ray of stomach after resection still shows markedly distorted and polypoid folds in gastric stump.

52

M. A. A-')pellberg, Lester Baker

Roentgenologic examination of the stomach revealed moderately severe polypoid hypertrophy of the gastric mucosa (Fig. 13). At gastroscopy a good deal of redness and irregularity of the antral mucosa was noted. In the midportion of the stomach, on the greater curvature posterior wall, several 0.5 cm. nodules were seen. The surface of the nodules appeared to be covered by normal epithelium, but dilated blood vessels were noted on the surface. The gastroscopic impression \vas hypertrophic antral gastritis. The nodules were suggestive of neoplasm, even though covered by epithelium and not ulcerated. An exploratory laparotomy with gastrotomy was recommended if the clinical state warranted such a procedure. On an adequate diet and vitamin supplements, the patient's clinical status

Fig. 13 (Case Ill, J. H. A.). X-ray showing filling defects especially on greater curvature of stomach suggestive of neoplasm.

improved and his symptoms completely disappeared. However, because of the questionable x-ray and gastroscopy findings, a laparotomy was performed. The stomach was normal in size and appearance except for some dilated venous channels traversing its anterior surface. On palpation it seemed slightly thicker and softer than normal although no polyps could be palpated externally. A number of hypertrophied lymph nodes were noted in the gastrocolic omentum and were removed for pathologic section. On opening the stomach, hypertrophied rugae were noted, several of which w"ere moderately indurated and the surface epithelium bled easily upon slight trauma. The biopsy revealed hyperplasia of gland structures with formation of large cysts (Fig. 14). Extensive infiltration of round cells and eosinophils were also noted (Fig. 15). The patient's postoperative course and subsequent hospital course were uneventful and he was discharged asymptonlatic. Serum protein determinations were, unfortunately, not performed on this patient.

Gastritis: Its Clinical

~gign,ificance

53

The clinical features of tumor-simulating gastritis present nothing distinctive. There is no predilection as to age since one of our patients was 28 and the other t\VO over 50. The symptomatology presents a vague dyspepsia or no gastrointestinal symptoms at all. However, some of the

Fig. 14 (Case Ill, J. H. A.). Microscopic section (X30) showing glandular hyperplasia and cyst formation.

Fig. 15 (Case Ill, J. H. A.). Microscopic section (X90) showing round cell infiltration between hyperplastic glandular structures.

54

M. A. Spellberg, Lester Baker

outstanding symptoms and findings may confirm the suspicion of malignancy. Among these are anorexia, weight loss, anemia47 , 49 and hypoproteinemia. The last finding may be accompanied by edema. One of our patients showed extreme weight loss to the point of cachexia, and two showed hypoproteinemia. In one it was so marked as to be productive of edema. The anemia may be due to the protein loss and the loss of blood in the stools from the friable and inflamed mucosa. Peripheral edema has been emphasized by others as occurring in this condition associated with a lowering of the total serum proteins. 23 Three possibilities have been postulated to explain the low proteins :48 1. Protein loss through abnormal mucosa into the gastric lumen. 2. A substance (s) elaborated by gastric lesion inhibits synthesis or storage of protein by either toxic or metabolic suppression. 3. The lesion may inhibit the stomach's ability to elaborate a factor (s) which facilitates synthesis or storage of protein. The gastric acidity may be normal or considerably lowered. The extent of acid production can be correlated with metaplastic replacement of acid-producing gastric cells by colonic tYPQ,J)f.m.~~o,,l~alt_ blli bean stated that complete achlorhydria is not a feature of this condition,49 in distinction to multiple polyposis of the stomach. 53 ANTRAL GASTRITIS

Gastritis involving the pyloric antrum is also important because of the possible roentgenographic confusion with neoplasm. The gastritis that can cause this confusion is usually hypertrophic gastritis with large or nodular rugal folds or the antral gastritis and deformity that may follow antral or duodenal ulcer. Occasionally superficial. gastritis by causing antral spasm can mimic carcinoma. The anxiety about the diagnosis in this region is heightened by the frequency of infiltrating neoplasms in the antrum which may give a similar clinical and roentgenographic picture. In order to make the correct clinical diagnosis, all the available diagnostic technics must be brought to bear on the problem. This includes an analysis of the clinical picture, such as loss of weight, anorexia, anemia, a search for occult blood in the stools, and a study of gastric acidity. While none of these features are crucial in themselves, like all diagnoses this one is to be arrived at by a preponderance of factors pointing in one direction or the other. Gastroscopy is quite important when the clinical and roentgenographic features are not clear enough to permit a definite diagnosis-and this is frequently the case in antral lesions. The gastroscope should afford a good deal of help in the diagnosis by demonstrating the character of the mu·· cosa and detecting the degree and character of peristaltic action. While

Gastritis: Its Clinical Significance

55

an isolated lesion on the lesser curvature of the antrum distal to the angulus cannot be visualized by the ordinary gastroscopic procedure, diffuse antral involvement should be clearly visible to the gastroscopist if he can pass the instrument into the distal portion of the stomach. The gastroscopic features which speak for a benign lesion are: (1) unimpeded peristaltic activity, (2) rugal folds which although enlarged are not stiff or infiltrated, as noted by their response to inflation, and (3) nodules if any, have an inflammatory appearance and (4) ulcers if present are either superficial or have the character of benign ulceration. In many of the 43 cases of antral gastritis that we observed during this period, the roentgenologist was unable to differentiate positively between gastritis and neoplastic infiltration. By using the above criteria we were able to dispel this doubt. In several cases exploratory laparotomy was resorted to not because of doubt on gastroscopy but because of the persistence of the suspicious roentgenographic picture. In all these cases the benignity of the process was confirmed by the surgical findings. We have noted repeatedly the greater accuracy of gastroscopic antral peristaltic activity as compared with roentgenographic observation. The following cases demonstrate some of the problems involved. CASE IV. * H. A., aged 65, entered the hospital in May 1942 complaining of epigastric distress and eructation of two months' duration. These symptoms occurred shortly after an appendectomy. Eructation and gaseous distention had been troublesome for many years but lately the gas was more difficult to expel. The symptoms were especially troublesome immediately after meals, but there was no nausea, vomiting or loss of weight. Physical examination was negative except for epigastric tenderness. X-ray examination of stomach by barium meal was reported as showing prepyloric narrowing and infiltration diagnostic of antral carcinoma. Exploratory laparotomy, in 1942, revealed a grossly thickened and redundant prepyloric mucosa, and a cirrhotic liver. The antrum was incised and a section was removed for biopsy. Microscopically, the biopsy showed glandular hyperplasia of gastric mucosa, but no evidence of tumor. This patient re-entered the hospital in March 1952, almost 10 years later. While most of her symptoms, such as distention and eructations, continued unabated, she had recently developed anorexia and a 6 pound weight loss. A mild secondary anemia was found with a hemoglobin of 9.7 gm. and 3,500,000 erythrocytes. X-ray at this time showed infiltration of the antrum as well as pars media. The antral infiltration extended down to the pylorus and resulted in pyloric obstruction with 30 per cent retention after 4 hours. Exploratory laparotomy in 1952, revealed a tumor occupying the entire antrum and obstructing the pylorus. Metastasis was noted in gastrocolic omentum and liver. Microscopic examination of one of the biopsied lymph nodes showed anaplastic carcinoma.

* This case is reported through the courtesy of Dr. Robert Lev y of Michael Reese Hospital.

56

M. A. Spellberg, Lester Baker

CASE V. J. K., a man aged 50, came in as an outpatient in September 1950 complaining of epigastric pressure and pyrosis coming on one to two hours afte; meals and vomiting several times a week, most frequently in the morning. The patient was moderately obese and showed no anorexia or weight loss. Gastric analysis showed the presence of free hydrochloric acid after histamine stimulation. X-ray examination of the stomach and duodenum showed a slightd~6rmity of duodenal bulb and small duodenal crater, and several ovalJilli~gvdefects suggestive of sessile polyps were seen in the antrum. The antral folds ~e'ie large. Gastroscopic examination revealed large antral rugal folds which were edem-

Fig. 16 (Case V, J. K.) .Compression "spot film" of antrum,,; showing large rugal folds radiating toward crater.

atous and hyperemic. One of these showed a red, poJypoid projection with a superficial ulceration at its apex. The patient became asymptomatic on an ulcer ~egimen and the x-ray as well as the gastroscopic picture showed marked improvement. He remained asymptomatic until December 1951, when epigastric pressure, vomiting and pyrosis recurred. There was no anorexia or weightloss. The x-ray at this time showed an antral crater with enlarged antral rug~Ctplds (Fig. 16). Gastroscopic examination was repeated and showed a marked hypertrophic antral gastritis with two ulcers, one on the anterior wall and one on the lesser curvature. Antral peristalsis was very active and the entire picture was interpreted as nodular hypertrophic antral gastritis and two benign gastric ulcers. The patient was continued on ulcer regimen and again became asymptomatic but in spite of this several months later repeat roentgenographic examination of stomach revealed distinctly the 2 ulcers which had increased in size (Fig. 17). Because of the lack of objective evidence of healing and because of the marked hypertrophic gastritis, surgery was advised. This the patient refused and further

Gastritis: Its Clinical Significance

57

medical therapy was attempted, without healing of ulcers. Gastric resection was final done 9 months after the first recurrence. Pathological examination of the resected specimen sho,ved 2 ulcers, hypertrophic gastritis and carcinoma-insitu.

Fig. 17 (Case V, J. K.). Three months after Figure 16. Two ulcers clearly visualized in spite of adequate medical therapy.

DISCUSSION

Cases IV and V both demonstrate some of the problems involved in the diagnosis of antral lesions. In Case IV the original x-ray impression }Va~ carcinoma and t.his. was disproved at operation. Unfor~unately no gastroscopic study wa~ done in this patient but it is likely t~a~ gastroscopy in 1942 may have resulted .in a correct interpretatiqn.:Case V ~e~ cause of the large antralrqgalfolqs., nodularityof muco~al pattern and ulceration c9uld' easily have been interpreted as neoplastic in nature. The gastroscopic picture was that. ·of "inflammation and benign ulceration ; however, because of persistence of both lesions, carcinoma was considered. Case IV raises a poignant question: Was the gastritis seen on. x~ray and microscopically in 1.942 a "preeancerous" lesion \vhich eventuated in carcinoma? And this -specific question may be expanded into the gen-

58

M. A. Spellberg, Lester Baker

eralization: Are certain types of hypertrophic gastritis and especially the giant variety precancerous lesions? This stomach in 1942 showed "glandular hyperplasia" at the same site at which the carcinoma appeared in 1952. Since in atrophic gastritis certain changes in the epithelium suggest the possibility of a precancerous state, there seems no valid reason for denying that a hypertrophic gastritis may have the same propensity. In this particular case the pathologist mentioned that some of the epithelium looked newly formed, which suggests variability in character of epithelium and a tendency to neoplasia (metaplasia). Case V likewise represents a severe gastritis with chronic ulceration and early carcinoma. In the giant rugal folds and tumor-simulating gastritis with hyperplasia of the glandular element and cyst formation it requires no flight of imagination to foresee the possibility of malignant metamorphosis. In one of our cases some of the glandular epithelium assumed the appearance of intestinal epithelium looked upon by Shields Warren 68 as a precancerous lesion. Other students of this problem in the past, among them Konjetzny, Schindler and Hurst, have assumed an etiologic relationship between certain forms of gastritis and gastric carcinoma. This relationship has also been emphasized by Meyers. 19 Recently Prinz 69 described 4 cases of one form of hypertrophic gastritis which resembled carcinoma clinically and microscopically consisted of marked lymphocytic infiltration, the so-called "chronic lymphatic gastritis" of Konjetzny. One of these 4 patients showed carcinomatous degeneration. Alvarez 60 reported the development of carcinoma fifteen years after a diagnosis of gastritis, and in another instance carcinoma was found eight years after a diagnosis of giant hypertrophic gastritis. 66 The report of Palumbo and co-workers 61 showing a gradual change from benign to malignant gastric mucosa is a striking example of this metamorphosis. This problem may have to await solution for the further development of the biopsy gastroscope. 62-66 This discussion is not intended to suggest that gastric carcinoma is always preceded by gastritis or that gastritis is a necessary precursor of carcinoma. However, the time-honored clinical concept that gastric carcinoma always occurs in a person without a previous history of dyspepsia is as false as the one that gastric carcinoma does not occur in patients with duodenal ulcer. In view of our·ignorance about the pathogenesis of gastric carcinoma, it is interesting to speculate that small groups of these dangerous lesions may arise on the soil of a pre-existing gastritis. TREATMENT The treatment of gastritis in general is a conservative dietary regimen and avoidance of irritants similar to the program used in peptic ulcer. The special varieties that simulate gastric neoplasms are frequently treated surgically because of diagnostic uncertainties. In view of the

remote possibility of carcinoma ata later date such drastic measures

(}astritis: Its Clinical Significance

59

might be justified. l"he severe hypoproteinemia in the giant hypertrophic gastritis req~ires special measure.s; high pr~tein diet and plasma infusions will raIse the plasma proteIns, but thIS may be only temporary. While some cases may be maintained in this manner surgery may be required for the grave hypoproteinemia. It is interesting that the proteins are well maintained after subtotal gastrectomy. Even total gastrectomy has been done. 48 X-ray therapy seems to be a logical therapeutic agent in these cases and this has been suggested. 54 We have no experience with it but one of the cases of Maimon and co-workers was unsuccessfully treated by this tneans. SUMMARY

1. The problem of gastritis is reviewed in general terms. 2. Among 886 gastroscopies, 547 showed some type of gastritis. 3. In our experience hypertrophic gastritis is the most frequent, and superficial gastritis next in. frequency. 4. The problems of giant hypertrophic (tumor-simulating) gastritis are analyzed and 3 cases of this rare entity are reported. 5. The diagnostic problems of antral gastritis are discussed and 2 illustrative cases are presented. 6. In one of the cases of antral gastritis proved by biopsy an antral carcinoma developed ten years later, and the other showed carcinomain-situ along with 2 benign ulcers. 7. The relationship between gastritis and carcinoma is discussed. REFERENCES 1. Sanchez-Palomera, E.: Concept of the Mucous Barrier and Its Significance.

11. Changes in the Gastric Mucosa Produced by the Local Actions of Spices and Other Irritative Agents. Gastroenterology 18: 269, 1951. 2. Faber, K.: Gastritis and its Consequences. London, Oxford IJniversity Press, 1935. 3. Wolf, S. and Wolff,H. G.: Human Gastric Function. London, Oxford University Press, 1943. 4. Schwartz, 1. R.: A Gastroscopic Study Following an Outbreak of Food Poisoning. Gastroenterology 6: 105, 1946. 5. Palmer, E. D.: The Morphologic Consequences of Acute Exogenous (Staphylococcic) Gastroenteritis on the Gastric Mucosa. Gastroenterology 19: 462, 1951. 6. Loughed, J. R. and Golding, F. C : The Gastric Mucosa in Acute Infectious Hepatitis. Gastroenterology 20: 471, 1952. 7a. Knight, W. and Cogwell, R. C.: Preliminary Observations of the Gastric Mucosa in Patients with Infectious Hepatitis. J .A.M.A. 128: 803, 1945. b. Bank, J. C. and Dixon, C. W.: Gastroscopy in Acute and Chronic Hepatitis. J.A.M.A. 131: 107, 1946. 8. Pollard, H. M. and Stuart, G. J.: Experimental Reproduction of Gastric Allergy in Human Beings with Controlled Observations on Mucosa. J. Allergy 13: 467, 1942. 9. Lichstein, J. and Benjamin, M.: Transient Allergic Gastric Edema: Report of Gastroscopic Observations During Asthmatic Attacks. Ann. Int. Med. 32: 967, 1950.

60

M. A.

~')pellberg,

Lester Baker

10. Eusterman, G. B. and Balfour, D. C.: The Stomach and the Duodenunl. Philadelphia, W. B. Saunders Co., 1936. 11. Boikan, W. S. and Singer, H. A.: Gastric Sequelae of Corrosive Poisoning. Arch. Int. Med. 46: 342, 1~)30. 12. Baker, L. and Spellberg, M. A.: Pyloric Stenosis Secondary to Hydrochloric Acid Ingestion. J .A.M.A., in press. 13. Schindler, R.: Gastritis. New York, Grune & Stratton, 1947. 14. Schindler, R. and Ortmayer, M.: Histopathology of Chronic (jastritis. Arn. J. Digest. Dis. & Nutrition 9: 411, 1942. 15. Guiss, L. W. and Stewart, F. W.: Chronic Atrophic Gastritis and Cancer of the Stomach. Arch. Surge 46: 823, 1943. 16. Magnus, H. A. and Ungley, C. C.: The Gastric Lesion in Pernicious Anemia. Lancet 1: 420, 1938. 17. Brown, M. R.: Pathology of the Gastro-intestinal Tract in Pernicious Anemia and Subacute Combined l)egeneration of the Spinal Cord; Study of 151 Autopsies. New England J. Med. 210: 473, 1934. 18. Cox, A. J.: The Stomach in Pernicious Anemia. Am. J. Path. 19: 491,1943. 19. Meyers, W. C.: A Study of Gastric Mucosa in Various Diseases Affecting the Upper Part of the Gastro-intestinal Tract. Gastroenterology 10: 923, 1948. 20. Kaplan, H. S. and Rigler, L. G.: Pernicious Anemia and 'Carcinoma of the Stomach-Autopsy Studies Concerning Their Interrelationship. Am. J. Med. Se., 209: 339, 1945. 21. Carey, J. B. and Hay, L.: Gastric Polyps. Gastroenterology 10: 102, 1948. 22. Ricketts, W. E. and others: Effect of Roentgen Irradiation of the Gastric Mucosa. Gastroenterology 11: 818, 1948. 23. Maimon, W. N. and others: Giant Hypertrophic Gastritis. Gastroenterology 8: 397, 1947. 24. Windholz, F.: The Roentgenologic Diagnosis of Hyperplasia of the Gastric Mucosa. Radiology 17: 514, 1931. 25. Cole, L. G.: Hypertrophic Gastritis. M. CLIN. NORTH AMERICA 17: 1,1933. 26. Renshaw, R. J. F.: Some Gastroscopic Observations in Gastric Ulcer. Clev. Clin. Quart. 7: 123, 1940. 27. Templeton, F. E. and Boyer, R. C.: The Diagnosis of Gastric Cancer. Am. J. Roentgenol. 47: 262, 1942. 28. Pollard, H. M. and Cooper, R. R.: Hypertrophic Gastritis Simulating Gastric Carcinoma. Gastroenterology 4: 453, 1945. 29. Ricketts, W. E. and Pollard, H. M.: A Roentgenologic and Ciastroscopic Study of Gastric Disease. Gastroenterology 6: 1, 1946. 30. Moersch, H. J.: The Gastroscopic Differentiation of Gastritis from Carcinoma of the Stomach. Gastroenterology 8: 284, 1947. 31. Benedict, E. B.: The Limitation of Roentgenology and Gastroscopy in the Diagnosis of Diseases of the Stomach. Gastroenterology 8: 251, 1947. 32. Patterson, H. A.: Massive Hypertrophic Gastritis. Ann. Surge 135: 646, 1952. 33. Baker, L., Gorvett, E. (1. and Spellberg, M. A.: Diagnostic Accuracy of Gastroscopy in Neoplasms of the Stomach. Cancer, in press. 34. Kantor, J. L.: Giant Rugae (Localized Hypertrophic Gastritis) Resembling Carcinoma. I{oentgenology 35: 204, 1936. 35. Feldman, M.: Giant Rugae with Hypertrophic (1astritis. Radiology 41: 181, 1943. 36. Spriggs, E. I. and Marxer, O. A.: Polyps of the Stomach and Polypoid Gastritis. Quart. J. Med. 12: 1, 1943. 37. Ricketts, W. E., Kirsner, J. B: and Palnler, W. L.: Large, ()therwise Normal Gastric Rugae Simulating Tumor of the Stomach. G-astroenterology 8: 123, 1947. 38. Moersch, H. J. and Weir, J. F.: Redundant Gastric Mucosa Simulating Carcinoma of the Stomach. Am. J. Digest. Dis. 9: 287, 1942. 39. Reeks, W. G. and Gibbs, W. T.: Gastric Polyposis. Report of a Case of Polyadenomes en nappe. Ann. Surge 115: 356, 1~)42.

Gastritis: I ts

Clir~ical ~'3ignificance

61

40. Schindler, R. and McGlone, F. B.: Familial Occurrence of Hyperplastic Gastric Polyps. Arch. Surg. 41: 1483, 1940. 41. Menentrier: Quoted by Heeks and Gibbs. 39 42. Schafer, P. W.: Pathology in General Surgery. Chicago, University of Chicago Press, 1950, pp. 290-295. 43. Bartlett, J. P. and Adams, W. E.: Generalized Giant Hypertrophic Gastritis Simulating Neoplasm. Arch. Surg. 60: 543, 1950. 44. Balfour, D. C.: Polyps of the Stomach. Surg., Gynec. & Obsta 28: 465,1919. 45. Eliason , E. L. and Wright, U. M. W.: Benign Tumors of the Stomach. Surg., Gynec. & Obsta 41: 461, 1925. 46. Marshall, S. F.: In discussion of paper by Patterson. 32 47. Freedman, f~., Glen, P. M. and Laipply, T. C.: Chronic Gastritis Simulating Gastric Carcinoma. Arch. Int. Med. 71: 23, 1943. 48. Balfour, D. C. and others: G-ian t Hypertrophy of the Gastric Rugae (Menentrier's Disease) Associated with Severe Hypoproteinemia Relieved Only by Total Gastrectomy. Gastroenterology 16: 773, 1950. 49. Forrester-Wood, W. R.: Giant Hypertrophic Gastritis. Brit. J. Surg. 37: 278, 1950. 50. Cox, A. J., Jr. and Barnes, U. R.: Experimental Hyperplasia of the Stomach Mucosa. Proc. Soc. Expel'. BioI. & Med. 60: 118, 1945. 51. Gill, M.: 1'roc. Royal Soc. of Med. (London) 38: 81, 1944. 52. Wood, 1. J. and others: The Relationship between Secretions of the Gastric Mucosa and Its Morphology as Shown in Biopsy Specimens. Gastroenterology 12: 949, 1949. 53. Sinclair, N.: Brit. J. Surg., 20: 645,1938. 54. Schindler, R.: Chronic Hypertrophic Ulcerative (}astritis Treated with Coutard's Method of Roentgen Therapy. Am. J. Digest. Dis. & Nutrition 3: 751, 1936. 55. Schindler, R., Benjamin, M. and Schlosberg, S. S.: Death from Cachectic Chronic Gastritis? Gastroenterology 14: 530, 1950. 56. Matzner, M. J., Raab, A. P. and Spear, P. W.: Benign Giant Gastric Rugae Complicated by Submucosal Gastric Carcinoma. Gastroenterology 18: 296, 1951. 57. Berne, C. J. and (jibson, W. R.: Giant Hypertrophic Gastritis. West J. Surg., Obsta & Gynec. 57: 388, 1949. 58. Warren, S. and Meissner, W. A.: Chronic Gastritis and Cancer of the Stomach. Gastroenterology 3: 251, 1944. 59. Christopher, F.: Malignant Diffuse Polyposes. Ann. Surg. 106: 118, 1945. 60. Alvarez, W. C.: Cancer of the Stomach Arising in Gastritis. Proc. Staff Meet., Mayo Clin. 18: 225, 1943. 61. Palumbo, L. T., Rugtiv, G. M. and Cross, K. R.: Giant Hypertrophic Gastritis. Its Surgical and Pathological Significance. Ann. Surg. 134: 259, 1951. 62. Shallenberger, P. L. and others: Biopsy Through the Flexible Operating Gastroscope. (j-astroen terology 16: 327, 1950. 63. Benedict, E. B.: Discussion on "Symposium on G-astroscopy." Gastroenterology 16: 354, 1950. 64. Shallenberger, 1'. L. and others: G-astroscopic Biopsy. Correlation of Clinical Findings and Tissue Biopsies of the Stomach. Rev. Gastroenterology 18: 348, 1951. 65. Wirts, C. W., CarroIl, J. L. and Wald, D.: ]~xperiences with the Operating Gastroscope. (jastroenterology 19: 777, 1951. 66. Wessell, M. S., Wilbur, l~. L. and Burger, R. A.: Acute Phlegmonous Gastritis. (jastroenterology 12: 884, 1949. 67. Spellberg, M. A. and Norfleet, W. J.: Early Gastrie Syphilis. Gastroenterology 2: 191, 1944. 68. Spellberg, M. A. and Zivin, S.: Lymphosarcoma of (iastrointestinal Tract. Arch. Int. Med. 83: 135, 1949. 69. Prinz, H.: Chronic Lymphatic Gastritis (Konjetzny): Clinical Significance and I{elation to Brill-Symmers Disease. Beitrage zur klin. ChiI'. 183: 129, 1951.